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Updated: Jun 14, 2026
07:26
Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis
Published on: April 1, 2022
KCTD1/KCTD15 complexes repress AP-2α and AP-2β to regulate neural crest-dependent craniofacial morphogenesis and
Jackelyn R Raymundo1, Bill Senapati1, Wenjuan Zhu2
1Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
The Journal of Investigative Dermatology
|June 12, 2026
Summary
KCTD1/KCTD15 complexes regulate craniofacial development by repressing AP-2 transcription factors in neural crest cells. Loss of this regulation causes aplasia cutis congenita (ACC) and related birth defects.
Area of Science:
- Developmental Biology
- Genetics
- Craniofacial Development
Background:
- KCTD1 and KCTD15 form complexes regulating neural crest cells (NCCs) and keratinocytes.
- Mutations cause aplasia cutis congenita (ACC) and craniofacial abnormalities, but in vivo mechanisms are unclear.
Purpose of the Study:
- Investigate KCTD1/KCTD15 complex function specifically in NCCs.
- Elucidate the downstream mechanisms of KCTD1/KCTD15 in craniofacial development and ACC pathogenesis.
Main Methods:
- Conditional mouse models
- Cell lineage tracing
- Genetic epistasis approaches
- Analysis of AP-2α and AP-2β transcriptional activity
Main Results:
- KCTD1/KCTD15 complexes repress AP-2α and AP-2β transcriptional activity in NCCs.
- Loss of KCTD1/KCTD15 in NCCs causes ACC, craniofacial, and scalp defects.
- Reduced AP-2α/AP-2β dosage rescues these defects, implicating derepressed AP-2 activity.
Conclusions:
- A KCTD1/KCTD15-AP-2 regulatory axis controls NCC-derived craniofacial and scalp development.
- ACC is a neurocristopathy resulting from dysregulated AP-2 activity in NCCs.
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